The long wait for a cellular and functional definition of canalicular transporters for biliary cholesterol appears to be over. Articles in this issue of the JCI provide a fascinating account of the cellular itinerary of two murine ATP-binding cassette (ABC) half-transporters from the ribosome to the hepatocyte apical membranes (1) and show that the corresponding human genes, when overexpressed in transgenic mice, can greatly augment cholesterol secretion into bile (2). This field was opened with the genetic solution (3, 4) to the enigma of a disease commonly known as sitosterolemia (5, 6). This autosomal recessive disorder of lipid metabolism is characterized by an accumulation of plant sterols, including sitosterol, in the plasma of patients with this disease and is therefore also known as phytosterolemia. Normally, the intestinal absorption of sitosterol and other unwanted plant sterols is dwarfed by the absorption of cholesterol, and the absorbed phytosterols are cleared from the body by highly efficient secretion into bile (5). However, patients with sitosterolemia display intestinal hyperabsorption of plant sterols and impaired biliary sterol secretion, leading to accumulation of phytosterols in the body (6). The metabolism of cholesterol is altered in the same manner, but to a lesser extent (5), rendering many patients hypercholesterolemic (6) and prone to xanthomas and premature atherosclerosis (5, 6). The dramatic consequences of this rare disease demonstrate the importance of a finely tuned mechanism for restricting the absorption and accumulation of ingested sterols. The underlying pathophysiological defects indicated that unraveling the molecular basis of sitosterolemia might shed light on important principles concerning intestinal sterol absorption as well as cholesterol secretion into bile. Two independent groups (3, 4) identified mutations in sitosterolemia patients in either member of an adjacent pair of genes, ABCG5 and ABCG8, encoding ABC transporters expressed in the liver and intestine (3, 4, 7). Functional ABC transporters consist of 12 membrane-spanning domains and two ATP-binding sites, whereas ABCG5 and ABCG8 are examples of half-transporters containing only six transmembrane domains and one ATP-binding site. Therefore, both teams of investigators (3, 7) suggested that ABCG5 and ABCG8 function as a heterodimer to limit intestinal sterol absorption by effluxing sterols from enterocytes to small intestinal lumen and by promoting hepatic sterol secretion into bile. Still, in the absence of direct evidence, the function of ABCG5 and ABCG8 and their subcellular localization remained hypothetical until now.